Platelet adhesion onto artificial surfaces: inhibition by benzamidine, pentamidine, and pyridoxal-5-phosphate as demonstrated by flow cytometric quantification of platelet adhesion to microspheres.
An appreciable effort is directed toward designing strategies to minimize platelet interactions with artificial surfaces, because their reactivity is thought to promote thrombus formation and lead to materials failure. Although platelet glycoprotein Ib/IX (GPIb/IX) and glycoprotein IIb/IIa (GPIIb/IIIa) receptors are thought to mediate adhesion, whether GPIIb/IIIa receptors are activated and how this might occur are largely unknown and are the focus of this article. There are a few ways, other than thrombin generation, that blood contact with artificial surfaces can lead to GPIIb/IIIa activation. Complement activation can lead to products capable of activating platelets (C1q, C5b-9), and contact between platelet CD32 (FcgammaRII) receptors and immobilized immunoglobulin G could also activate platelets. In this article the potential role of these processes was evaluated by using various inhibitors in a microsphere-based platelet adhesion immunoassay. Polystyrene microspheres (10 microm) were incubated in platelet-rich plasma before flow cytometric analysis of beads for adherent platelets. The data eliminated occupancy of the FcgammaRII receptor (by use of IV.3 blocking antibody), C5b-9 production (by use of sCR1), and the indirect action of factor XIIa on complement components (by use of corn trypsin inhibitor) as playing roles in supporting platelet adhesion. Agents directed against the first complement component (benzamidine, pentamidine, pyridoxal-5-phosphate) were effective inhibitors of platelet adhesion and were also demonstrated to inhibit SC5b-9 and C3d levels on the bead surface after serum incubations. Because these agents are not highly specific, it can not be concluded that C1q is a mediator of adhesion. These agents were also demonstrated to inhibit fluorescein isothiocyanate-fibrinogen binding to activated washed platelets, therefore indicating that fibrinogen receptor expression is a requirement for platelet adhesion.
Gemmell
C H
CH
Department of Medicine, University of Toronto, Ontario, Canada.
D001550:Benzamidines / Q000494:pharmacology*; D003167:Complement Activation; D015933:Complement C3d / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000378:metabolism; D003165:Complement System Proteins / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D005434:Flow Cytometry; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D008863:Microspheres; D010419:Pentamidine / Q000494:pharmacology; D010973:Platelet Adhesiveness / Q000187:drug effects*; D011095:Polyethylenes; D011732:Pyridoxal Phosphate / Q000494:pharmacology*; D011951:Receptors, Complement / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism
D001550:Benzamidines; D015938:Complement Membrane Attack Complex; D006023:Glycoproteins; D011095:Polyethylenes; D011951:Receptors, Complement; D017452:Receptors, IgG; C047610:SC5b-9 protein complex; D011732:Pyridoxal Phosphate; D010419:Pentamidine; D015933:Complement C3d; D005340:Fibrinogen; D003165:Complement System Proteins; C032157:benzamidine